Work

Baicalin-geniposide attenuates pulmonary inflammation and vascular injury via HMGB1 blockade: insights from a cerebral ischemia-reperfusion model and implications for pulmonary hypertension

Year: 2026

Type: article

Abstract: Introduction Pulmonary complications following stroke are a leading cause of death, with no targeted therapies available. Inflammation drives both post‐stroke neurological damage and secondary acute lung injury (CIS-ALI). High mobility group box 1 (HMGB1), a key mediator in cerebral ischemia stroke (CIS), translocates from the nucleus to cytoplasm and is released extracellularly, triggering inflammatory cascades. The combination of two bioactive metabolites, baicalin and geniposide (BG), exhibits anti‐inflammatory and neuroprotective properties, but its efficacy against CIS-ALI remains unexplored. This study investigated BG’s mechanisms using in vitro and in vivo models. Methods This study investigated the mechanisms of BG using in vitro and in vivo models. In vitro , LPS‐stimulated BV2 microglia and RAW264.7 macrophages were co‐cultured. In vivo , a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) was used. BG was administered at doses of 25—50 mg/kg in rats. Results BG dose-dependently suppressed pro-inflammatory cytokines (TNF‐α, IL‐1β, IL‐6) and nitric oxide (NO), while attenuating HMGB1 nucleocytoplasmic translocation via JAK2/STAT3 inhibition. BG (25—50 mg/kg) reduced cerebral infarct volume, neurological deficits, and lung edema. Mechanistically, BG blocked HMGB1 nuclear export in ischemic brains, thereby decreasing HMGB1 levels in serum and lungs, and disrupting inflammatory cross-talk. Discussion These findings highlight BG’s unique capacity to concurrently mitigate cerebral injury and secondary ALI by targeting the JAK2/STAT3 axis, offering a safe, multi‐targeted strategy against CIS‐related complications. Given the shared pathological features between ALI and PH–including inflammation, vascular hyperpermeability, and JAK2/STAT3‐driven injury cascades–these findings provide a mechanistic rationale for exploring BG as a potential therapeutic candidate for pulmonary hypertension and related pulmonary vascular diseases.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1822890

Authors: Leying Gao, Qianqian Wu, Xiaoqiu Li, Yu Long, Nan Li

Institutions: Chengdu University of Traditional Chinese Medicine, University of Electronic Science and Technology of China, Mianyang Central Hospital

Language: English

Topic: Flavonoids in Medical Research

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801